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Molecular quantum similarity measures as an alternative to log P values in QSAR studies

Abstract:

A new molecular descriptor of hydrophobicity based on molecular quantum similarity measures (MQSM), which can be used to replace the log P parameter in QSAR studies, is proposed. Unlike the majority of existing approaches for calculation of log P, the present methodology does not rely on the use of fragment additive contributions, but rather it is based on the comparison of quantum chemically calculated electron density distributions of a given molecule in water and in 1-octanol, using MQSM. The method has been tested on a broad series of 58 molecules including such structural types as aliphatic hydrocarbons, alcohols, amines, halides, carboxylic acids, esters, amides, and ketones, as well as more complex systems with two functional groups. In all cases investigated, an excellent linear relationship between calculated MQSM and log P values was found. Additionally, an example of QSAR analysis is presented using MQSM instead of log P values, corresponding to pbkp_redict the narcosis of tadpoles. © 1998 John Wiley & Sons, Inc.